Physiol Behav. Umbhali wesandla; iyafumaneka kwi-PMC 2012 Oct 24.
Ishicilelwe kwifomu yokugqibela ehleliweyo njenge:
IPhysol Behav. I-2011 Oct 24; I-104 (5): 865-872.
Ipapashwe kwi-intanethi ye-2011 ngoMeyi 24. doi: 10.1016 / j.physbeh.2011.05.018
PMCID: PMC3480195
I-NIHMSID: I-NIHMS299784
UMiriam E. Bocarsly,1 ULaura A. Berner,1 U-Bartley G. Hoebel,1 kwaye UNicole M. Avena1,2
Abstract
Izifundo zangaphambili zibonisa ukuba ukutya iswekile okukhokelela kwisimo sokuziphatha kukutshintsha kokuziphatha kunye ne-neurochemical efanayo naleyo ibonwa kukungathengiswa iziyobisi, kubandakanya neempawu zokurhoxa okufana nokuqhawulwa. Izifundo ziyavela ezibonisa ii-neurochemical kunye neendlela zokuziphatha zeziyobisi xa izilwanyana zitya ukutya okunamafutha kakhulu. Injongo yesifundo esikhoyo yayikukusebenzisa amanzi kunye nokutya okuqinileyo okuneswekile nangamafutha ukumisela ukuba ukurhoxa okunje nge-opiate kubonwa emva kokuzinkcinkca kokutya kwezi rats kwa Sprague Dawley. Amaqela olawulo anikwa ad adum ukufikelela kukutya okunamafutha amnandi okanye i-standard standard. Zonke iigundane emva koko zanikwa ibhetri yovavanyo yokulinganisa iimpawu zokurhoxa okufana ne-opiate, ebandakanya iimpawu ezizezomntu oxinzelelo, uxinzelelo oluphakamileyo lwe-maze, kunye ne-locomotor hypoactivity. Nokuba i-naloxone-preipended (i-3 mg / kg) okanye ukurhoxiswa okungakhathalelwanga kwabonwa kwiigundane ezazigcinwe kwisondlo esipheleleyo esine-pelleted yokutya okunamafutha amnandi, ukutya okumnandi, okunamafutha aphezulu axhonywe nge-rodent chow esemgangathweni, okanye isiselo esimnandi- ukutya okunamafutha. Ukongeza, ukunciphisa ubunzima bomzimba ukuya kwi-85%, eyaziwa ngokuba nefuthe lokuqiniswa kwento yokuxhatshazwa, ayizange ichaphazele ne-lexone-precipended dalili zokurhoxiswa okufana ne-opiate. Ke ngoko, ngokungafaniyo neziphumo zangaphambili ebezixeliwe malunga namagundane anokufikelela ngokungxama kwisisombululo se-sucrose, iigundane eziziluma zitya ukudityaniswa kwamafutha amnandi azibonisi zimpawu zokurhoxa okufana nokupheliswa phantsi kweemeko ezivavanyiweyo. Ezi datha zixhasa umbono wokuba ukusebenzisa kakhulu izakhamzimba ezahlukeneyo kunokubangela ukuba kubenakho ukuzibandakanya ngeendlela ezahlukeneyo, kwaye isimilo esinokuphawula ukuba "kukungabinanto yakutya" sinokupheliswa ngokusekwe kulungelo lokutya okutyiwayo.
intshayelelo
Iinkqubo ze-Neural ezikhuthaza kwaye zomeleza ukufuna ukutya kunye nokutya kunye nokuziphatha okungaphantsi kokudibaniswa nokusetyenziswa gwenxa kweziyobisi [1-5]. Ngokusekwe koluhlu lwe-neurological, kuye kwacetyiswa ukuba ukusetyenziswa kokutya okuthile kunganeziphumo zokuziphatha okufana nokulutha [6-8]. Izifundo zangaphambili ezivela kwilabhoratri yethu kunye nezinye ziphakamisa ukuba ukufikelela okulinganiselweyo kwiswekile kukhokelela kutshintsho lweendlela zokuziphatha kunye notshintsho kwi-dopamine (DA) kunye neenkqubo ze-opioid ezifanayo, nangona zincinci ngobukhulu, kwezo zibonwa ngexesha lokusetyenziswa kweziyobisi [8].
Kwezi ndlela zokuziphatha ezinjengeziyobisi ezinxulunyaniswa nokusela kakhulu iswekile, ubungqina bokurhoxa-ngokufana nokutsala umdla kunomdla. Sebenzisa imodeli yethu yesilwanyana eselabhoratri yokutya iswekile, sifumanise ukuba xa ilawulwa i-opioid antagonist naloxone, iigundane zibonisa iimpawu ezithile zokurhoxa, kubandakanya nokuncokola kwamazinyo, ukuthuthumela, kunye nentloko, kunye noxinzelelo oluphakamileyo lwendibaniselwano. . Ngapha koko, ezi ndlela zokuziphatha zidityaniswa kunye nokwehla kokukhutshwa kwe-DA kwii-nucleus accumbens kunye nokwanda kokukhutshwa kwe-acetylcholine [9], ukungalingani kwe-neurochemical eye yabonwa ngexesha lokurhoxiswa kweziyobisi ezininzi zokuxhatshazwa [10, 11]. Iimpawu zokuziphatha kunye ne-neurochemical zokurhoxa okufana ne-opiate nazo ziye zajongwa ngaphandle kokusebenzisa i-naloxone (okt, ngokuzenzekelayo) ngokulandela ngokukhawuleza kwiigundane ezinembali yokutya kakhulu iswekile [12]. Abanye baqaphele ukuba iigundane ezinembali yokufikelela okuneshukela kunokwehla kobushushu bomzimba xa iswekile ikhutshiwe ngenxa ye-24 h [13] kwaye abonise iimpawu zokuziphatha gwenxa [14], zombini ezamkelwayo ziimpawu zokurhoxa. Ngapha koko, ukutya okuneswekile eninzi kubonisiwe ukuba kunokubakho iimpawu zoxinzelelo kunye ne-hyperphagia ebonakala ngathi iphakathi kweenkqubo zekamva ze-corticotrophin-ikhulula i-hormone [15].
Olunye uphononongo luye lwavavanya iinkalo zokwenza iziyobisi ezinokuthi ziphakame ekuphenduleni kokunye ukutya okuthandekayo, njengaleyo ityebileyo kumanqatha okanye kukudibanisa amafutha amnandi. INaloxone iye yanikelwa ukuba ivelise iimpawu zokurhoxa ezinje ngee-roses zityiswe isidlo esine-cafeteria, esinezinto ezahlukeneyo zokutya ezinamafutha- kunye neswekile [16]. Kutshanje, kubonisiwe ukuba iintonga ezivezwe ekutyeni ezityebileyo ziya kubandakanyeka kwiimpawu ezininzi zokuziphatha ezigwenxa [11, 17-19], kodwa ukubakho kokurhoxa okunjenge-opiate akufundiswanga ngokucwangcisiweyo ngaphakathi komxholo wokutya kakhulu i-oyile, kwaye akukho kwimeko yokufikelela kweshedyuli.
Ngenxa yokuba omabini amanqatha kunye neswekile kuchaphazela iinkqubo ze-opioid [3], ukuba ezi macronutrients ngamanye amaxesha zichithwe ngokugqithileyo kwaye zinokuba nenxaxheba kukukhuluphala okunxulunyaniswa nokutya kakhulu [20, 21] kunye nokuba likhoboka lokutya [22, 23], injongo yesifundo esikhoyo yayikukufumanisa ukuba ukurhoxa okunjenge-opiate ibonwa kwiigundane zigcinwe kwishedyuli yokufikelela okuncinci kokutya okuneshukela kunye namafutha akhokelela ekutyeni kakhulu. Ngeendlela ezininzi, olu luyilo luhambelana nemeko yokutya yomntu, njengoko iziqendu ezixhaphakileyo kwabanye abantu zihlala ziquka ukudityaniswa kwezi macronutrients [20, 21, 24, 25]. Ngapha koko, isifundo esikhoyo sivavanya isiphumo sokutya okungafunekiyo ekudityeni iswekile enamafutha-emzimbeni kunokubakho ekurhoxisweni xa iigundane zikwimeko yomzimba eqhelekileyo kwaye incitshisiwe, kuba kuyaziwa ukuba ubunzima bomzimba obuphantsi bunokubangela iziphumo zamachiza ukuhlukunyezwa [26]. Ngapha koko, iigundane ezinomzimba ophantsi okhupha i-DA ngakumbi kuneendlela eziqhelekileyo zokulawula ubunzima xa usitya kakhulu iswekile [27], enokubonisa isiphumo esonyuselweyo somvuzo kumzimba ophantsi onokuthi uchaphazele ubungqangi bokuzikhupha.
Impahla nenkqubo
Iindlela ngokubanzi
Iigundane ze-Male Sprague-Dawley zafunyanwa kwiifama zeTaconic (iGermantown, NY) kwaye zigcinwa zodwa kwiPriveton University vivarium kwi-12-h yokukhanya okuguqukayo: 12-h umjikelo omnyama. Igumbi laligcinwe kwi-20 ° ± 1 ° C, kwaye izilwanyana zazinayo ad adum ukufikelela kwamanzi ngalo lonke ixesha kunye nokufikelela kwilabhoratri esemgangathweni, iLabDiet #5001 (PMI Nutrition International, Brentwood, MO; 3.02 kcal / g) njengoko kuchaziwe ngezantsi. Zonke iinkqubo zamkelwa yiKholeji yasePrinceton yoKhathalelo lweZilwanyana kunye neKomiti yokuSetyenziswa. Ukutya kunye neenkqubo zishwankathelwe 1 Table.
Ukukhupha I-1: Ukuvavanywa kwe-Naloxone-yacaciswa kwaye yavela njengesiqhelo yokutsalwa kwe-rats kwiigundane ezondliwa ngokutya okunesondlo, okunamafutha neswekile
Iigundane (i-315-325 g) yahlulahlulwe yangamaqela amane anomzimba obunzima (n = 10 / iqela) kwaye yabelwa enye yezi meko zilandelayo zokondla kwiintsuku ze-25: (a) I-2-h ukufikelela kwemihla ngemihla kwi-inot-fat chow (Uphando Ukutya, i-New Brunswick, NJ, #12451; i-45% inqatha, i-20% iprotein, i-35% i-carbohydrate, i-4.7 kcal / g) iqala i-6 h emva kokuqala komjikelo wobumnyama, kunye ne-rodent esemgangathweni efumaneka kuphela kwi-22 h nganye usuku; (b) Ukufikelela kwi-2-h kwindawo yokutya okunamafutha amnandi ngoMvulo, ngolwezithathu, nangoLwesihlanu (MWF) nge ad adum ukufikelela kwi-rodent ye-standard ngexesha lokutsala kwexesha; (c) ad adum amanqatha amnandi; kunye (d) ad adum standard chow (LabDiet #5001, PMI Nutrition International, Richmond, IN; 10% fat, protein 20%, 70% carbohydrate, 3.02 kcal / g). Ukutya kwathathelwa indawo kabini ngeveki. Ukutya ukutya bekulinganiswa yonke imihla (ngaphambi nasemva kwexesha lokungena le-2-h, okanye ixesha elilinganayo le ad adumamaqela -fed). Ubunzima bomzimba bukwalinganiswa ngeli xesha ngeentsuku 1-7 kunye neentsuku 18-24 yokufikelela.
1a. I-Naloxone yahlola ukurhoxisa ukurhoxa
Ngeentsuku i-26 kunye nee-27 iigundane zabelwa ngokungaqhelekanga kuvavanyo lweempawu zokurhoxa. Ezi mvavanyo zasasazeka ngaphezulu kweentsuku ze-2 zokuqinisekisa ukuba iimvavanyo ziqhutywa kufutshane nesiqalo sexesha eliqhelekileyo le-2-h lokufikelela kumgangatho ngamnye. Ukuvavanywa kweempawu ezithile zokurhoxa kwe-opiate-like, iigundane zazilawulwa i-opioid antagonist naloxone (Sigma, St. Louis; 3 mg / kg, sc). Ukufakwa kwezitofu kwenziwa nge-6 h emva kokuqala komjikelo wobumnyama, xa ukufikelela kokutya okuthandekayo kuya kuqala ukuqala. Amagundane kwiqela le-2-h MWF ngokufuthi ayenexesha le-46-h lokunciphiseka okukhoyo phakathi kwamaxesha okungena phakathi evekini (nangona ayenendawo esemgangathweni ekhoyo ngeli xesha), kwaye nawo ayencitshiswa ukutya okuthandekayo ngeempelaveki. Ke, ukumisela umgangatho wexesha lokuncitshiswa kwe46-h, saqinisekisa ukuba zonke iigundane ezivavanyiweyo zazine-46 h yokuncothiswa kwamafutha amnandi. Kwimizuzu elishumi emva kwenaliti, iigundane zabekwa kwikheji elenziwe ngeplastiki neBhedi-o-Cobs (The Anderson Co, Maumee, OH), kunye neempawu zokurhoxa zarekhodwa kwimizuzu ye-5 ngumntu obonayo ongaboniyo kwiimeko zovavanyo. I-Institution of paw-biting, defense burginging, i-wet-hand shake, meno athetha, ukuhlunguzelwa yintloko, ukungcwatywa kwangaphambili, ukuwela ikheji, kunye nokuzilawula kwabhalwa kumgangatho ngamnye, kwaye iimeko zizonke zokuziphatha zazishwankathelwe ukuvelisa inqaku elipheleleyo lokurhoxa , usebenzisa indlela eguqulwe kwezinye iingxelo [28, 29].
1b. Uvavanyo lokurhoxa okuzenzekelayo
Ukufumanisa ukuba ngaba ukurhola ukurhoxiswa kunokubonwa ngokususa nje ukutya okuthandekayo (okt, ngaphandle kwe-naloxone), iigundane emva koko zanikwa ukufikelela kumgangatho kuphela we-rodent chow kwiiveki ze-3. Emva koko, iigundane zabuyiselwa kwiishedyuli zazo zangaphambili zokutya kwiintsuku ze-14. Ngexesha elalandelayo lokuthotywa okunamafutha amnandi, zonke izilwanyana zagcinwa kwi-rodent chow esemgangathweni ye-46 h. Ekupheleni kwe-46 h, xa iqela lokulinga lalihlala lifumana ukufikelela kwi-oy-fat-oy, endaweni yoko bavavanywa iimpawu zokurhoxa.
Ukukhupha I-2: I-Naloxone-yacekiswa kwangaphambili kunye novavanyo lokurhoxa oluzirholayo kumagundane elondliwe ngeseententent yokutya ngokutya okungaphelelanga kwesondlo okutyebileyo ushukela kunye namafutha
Olu vavanyo lusebenzise kuvavanyo okongeziweyo njengokurhoxa okufana ne-opiate, kunye ne-maze efanelekileyo, ukumisela iimpendulo ezizodwa kunye nexhala njengokurhoxa ekutyeni okuthandekayo. Iigundane (350-400 g) zahlulahlulwe zangamaqela amathathu anomlinganiso wobunzima (n = 8 / iqela) kwaye zagcinwa kwi ad adum chow kunye namanzi axhaswe koku kulandelayo kwiintsuku ze-28: (a) Ukufikelela kwe-12-h kumxube we-sukari eninzi, umxube wamafutha aphezulu (4.48 kcal / g; 35.7% fat, 64.3% sucrose; ibhotolo, iswekile enevumba, kulungiswe kwelethu elebhu); (b) ad adum ukufikelela kwiswekile efanayo nakumxube wamafutha (c) ad adum chow. Ukutya kwakutshintshwa kabini ngeveki, ngamanye amaxesha izilwanyana zazisindwa.
2a. Uvavanyo lokurhoxa okuzenzekelayo
Ngomhla we-28, zonke iigundane zabekwa kwindawo yokutya ad adum standard rodent chow. I-24 h kunye ne-36 h kamva zonke iigundane zavavanywa kwiimpawu ezithile zokurhoxa okunjenge-opiate-ukwenzela ukumisela isalathiso sokurhoxa, njengoko kuchaziwe kwi-Exp. 1a. Ke, ukuvavanya uxinzelelo, izilwanyana emva koko zabekwa ngokukodwa kwi-5 min kwindawo ephakanyisiweyo ye-maze [30]. Isixhobo sasineengalo ezine, nganye kwi-10 cm ububanzi nge-50 cm ubude, kwaye yayiphakanyiswe ngo-60 cm ngaphezu komgangatho. Iingalo ezimbini ezichaseneyo zavalelwa ngeendonga eziphezulu eziphezulu, ngelixa ezinye iingalo zazingenazindonga zokukhusela. Oluvavanyo lwenziwe phantsi kombane obomvu ukunciphisa ukuphazamiseka kumjikelezo weegundane. Iigundane zabekwa embindini we-maze eneentloko ezijijekileyo zatshintshelwa kwingalo evulekile okanye evaliweyo. Isilingo ngasinye sokudibanisa sidityaniswe ngevidiyo kwaye kamva safumana amanqaku kangangexesha elichithwe entloko, amagxa kunye nengalo yangaphambili engalweni evulekileyo, ingalo evaliweyo okanye icandelo leziko le-maze ngumbonisi ongaboniyo ngemeko yokutya.
2b. Uvavanyo lokurhoxiswa kweNaloxone
Ukulandela ukuvavanywa kwi-Exp. I-2a, zonke iigundane zabuyiselwa kukutya kwazo okwabelwe ukutya kwiintsuku ze-21 emva koko zalawulwa nge-naloxone (Sigma, St. Louis; 3 mg / kg, sc). Imizuzu elishumi emva kwenaliti, iigundane zajongwa njengezimpawu ezithile zokurhoxa kunye nokuphakanyiswa okukhathazayo kwe-maze (njengoko kuchaziwe kwi-Exp. 2a).
Ukukhupha I-3: Uvavanyo lokurhoxiswa kwe-ntuxone-okunamanzi okwahlanjwa kwiigundane zigcinwa kwi-rodent chow esemgangathweni kunye nokutya okulamanzi okunetyiwa ushukela namafutha.
Ukutya okuvavanywayo kwi-Exp. I-1 kunye ne-2 beziqinile; emva koko siye kuvavanya ukutya okuselulwelo ukwenzela ukulawula iimpembelelo zokufakelwa, kuba iimpawu zokurhoxa okunjengomntu kwisimo sethu sezilwanyana sokutya iswekile kubandakanywa nokusetyenziswa kwesisombululo se-sucrose [8, 9], kwaye kukho umahluko owaziwayo kwiimpembelelo ezinokuthi ukutya okuqinileyo kunye nolwelo kube nokuziphatha okungaphakathi [31, 32]. Iigundane (i-300-375 g) yahlulahlulwe yangamaqela amane ahambelana nobunzima (n = 8 / iqela) yagcinwa ngeentsuku ze-28 ngomhla ad adum i-chow eyongezwe: (a) ukufikelela kwe-12-h ukuya kwi-emulsion ye-oyile, iswekile kunye namanzi (3.4 Kcal / mL, 35% fat, 10% iswekile; Mazola® Ioyile yeOr, iscrose, amanzi ompompo kunye ne-0.6% Emplex, Izithako zeCaravan , I-Lenexa, KS, elungiselelwe elebhu yethu), kunye ne-chow; (b) I-12-h yokufikelela kwiVanilla Qinisekisa (i-1.06 Kcal / mL, i-30% inqatha, kunye ne-30% iswekile, iiLabhoratri zeLabhoratri, i-Abbott Park, IL) kunye ne-chow; (c) 12-h ukufikelela kwisisombululo se-10% (w / v) sucrose (0.4 Kcal / mL) kunye ne-chow, okanye (d) ad adum chow. Ukulungiselela i-emulsion, amanzi ayeshushu kwi-75-80 ° C kwaye kongezwa kwezinye izithako. I-emulsion ixutywe kwisantya esiphezulu se-5 min emva koko yaphola kwindawo yokuhlambela yomkhenkce de yaya kufika kwi20 ° C. Zonke izidlo (ngaphandle kwe-chow esemgangathweni) zazingamanzi kwaye zinikezelwa kwityhubhu yokusela yokugqiba. Ukutya kwakutshintshwa yonke imihla kwaye izilwanyana zazinxitywa iveki.
Uvavanyo lokurhoxiswa kweNaloxone
Emva kweentsuku ze-28 kwisidlo esinikiweyo, iigundane zazilawulwa nge-naloxone (3 mg / kg, sc). Imizuzu elishumi emva kwenaliti, iigundane zabekwa kwi-plus-maze ephakanyisiweyo njengoko kuchaziwe kwi-Exp. 2a. Ngokukhawuleza emva kovavanyo lwe-5-min oluphakanyisiweyo kunye ne-maze, iigundane zabekwa kwigumbi lekhompyuter, kwigumbi elinomsebenzi ovulekileyo ophantsi kokhanyiso olubomvu (I-MED Associates, Georgia, VT, 30.5 cm ukuphakama kwamacala e-acrylic kunye neefoto ze-16 infrared kwifoto nganye ye-axes ). Yonke intsimi yayiyi-43.2 cm × 43.2 cm. Umlinganiso ngamnye ekuqaleni ubekwe embindini webala elivulekileyo kwaye wanikwa ixesha lokuncamathiswa kwe10 min ngaphambi kokuvavanywa [33, 34]. Emva koko, umsebenzi we-locomotor, ochazwa njengemigqomo ye-infrared beam, wabekelwa iliso kwimizuzu ye-20.
Ukukhupha I-4: Uvavanyo lwe-opiate olufana noluxutyiweyo-njengokurhola ukurhoxiswa kwamagundane ngokunciphisa umzimba
Ukuvavanya ukuba ngaba iimpawu zokurhoxa zinokuphakanyiswa kumzimba oncitshisiweyo, iigundane ezinesisindo (283-345 g) zigcinelwe iintsuku ze-21 ngo: (a) I-2-h ukufikelela kwemihla ngemihla kwi-kop-fat chow (Ukutya okutyayo, I-Brunswick entsha, NJ, #12451, njengoko isetyenziswa kwi-Exp. 1) ukuqala i-6 h emva kokuqala komjikelo wobumnyama, kunye ne-rodent chow esemgangathweni efumaneka kuphela enye i-22 h ngemini (n = 10), okanye (b) ad adum i-standard ye-chow ene-2 h yokufikelela kwi-choc-fat elim kuphela kwiintsuku ezimbini (usuku lwe-2 kunye nomhla we-22 okanye i-23; I-Acute Sweet-Fat group, n = 9). Ukutya ukutya kukalwa imihla ngemihla kwi-6 h kunye ne-8 h emva kokuqala komjikelo wobumnyama; ukutya kwathathelwa indawo kabini ngeveki.
4a. Uvavanyo oluqhelekileyo lokurhoxisa ubunzima bomzimba
Ngomhla we-22, i-6 h kwixesha elimnyama, zonke iigundane zazilawulwa nge-naloxone (3 mg / kg, sc). Imizuzu elishumi emva kwenaliti, iigundane zajongwa njengezimpawu ezithile zokurhoxa kunye nokuphakanyiswa kwe-plus-maze njengoko kuchaziwe kwi-Exp. 2a.
4b. Uvavanyo lokunciphisa ukuthoba umzimba
Iigundane ze-2-h zemihla ngemihla i-Sweet-Fat rats ziye zancitshiswa ukuya kwi-85% ubunzima bomzimba ngaphezulu kwexesha leentsuku ze-7 ngokunciphisa ukubakho komgangatho oqhelekileyo wemihla nokuba yeyiphi-pellet (3 g) okanye ipellet enye (5 g) kunye ne-fat-fat chow sisiqingatha se-pellet (2 g) okanye ipellet enye (3.5 g). Isixa sokutya esinikiweyo kwalungiswa kumgangatho ngamnye kuxhomekeke kwinqanaba lokulahleka kwesisindo. Iqela le-Acute Sweet-Fat lancitshiswa laya kwi-85% yomzimba ngaphezulu kwexesha leentsuku ze-7 ngokunciphisa ukubakho komgangatho we-chow kwansuku zonke kwi-1-2 pellets. Iigundane kweli qela zinikwe i-2-h ukufikelela kwi-oy-enamafutha amnandi okwesithathu ngosuku 30 okanye 31. Uvavanyo lokurhoxa (imiqondiso ye-somatic kunye ne-maze) yenziwa kwakhona ngemini ye-29 njengoko kuchaziwe kwi-Exp. I-1a kunye ne-2a.
4c. Uvavanyo lomthamo womzimba oqhelekileyo
Emva kokuvavanywa ngokunciphisa umzimba, zonke iigundane zanikwa ad adum ukufikelela kwi-chow esemgangathweni yenyanga enye ukubavumela ukuba babuyele kubunzima bomzimba obuqhelekileyo kwiminyaka yabo. Ke, zonke izilwanyana zabuyiselwa kukutya kwazo kovavanyo kwiintsuku ze-14. Iigundane kwiqela le-Acute Sweet-Fat zinikwe ithuba lokufumana i-oy-fat-oy kwakhona ngomhla weshumi elinesine wokufumana ukutya okuvavanywayo ukuze kuqinisekwe ukuba indlela yokuziphatha ibangelwa kukutya kakhulu okanye ukubonwa nje kukutya. Ke, i-6 h emva kokuqala komjikelo wobumnyama, i-naloxone (3 mg / kg, sc) yenziwa. Imizuzu elishumi emva kwenaliti, iigundane zabekwa kwigumbi lekhompyuter, kwigumbi lomsebenzi wentsimi evulekileyo phantsi kokukhanya okubomvu, njengoko kuchaziwe kwi-Exp. 3a. Umlinganiso ngamnye ekuqaleni ubekwe embindini wegumbi locomotor, kwaye ukubalwa kwemisebenzi kwakulinganiselwa ngemizuzu ye-10.
4d. Ukunciphisa ubunzima bomzimba we-locomotor
Ukulandela uSm. I-4c, ubunzima bomzimba bazo zonke iigundane ziphinde zancitshiswa zaya kwi-85% njengoko kuchaziwe apha ngasentla ngeentsuku ze-7. Ukuvavanywa komsebenzi we-locomotor emva koko kwenziwa njengoko kuchaziwe kwi-Exp. 3c.
Uhlalutyo lweSatisati
Idatha yahlaziywa kusetyenziswa indlela enye kunye nohlalutyo lweendlela ezimbini ezahlukeneyo (ANOVA) ngovavanyo lwe-postman ho-Newman Keuls okanye lweTukey xa kufanelekile, okanye iimvavanyo zoMfundi. Ngedatha ephezulu ye-maze, imisebenzi yengalo evulekileyo yathathelwa ingqalelo njengexesha elipheleleyo elichithwe yi rat nganye kwimikhono evulekileyo ye-maze [35]. Idatha ye-locomotor yahlalutywa kuqala nge-ANOVA yendlela enye kumgangatho ngamnye we-locomotion kwaye emva koko ngeendlela ezimbini ze-ANOVA ukuthelekisa amanyathelo eqela le-locomotor kwinqanaba eliqhelekileyo kunye nelincitshisiweyo, kunye namanyathelo aphakathi kweqela. Impazamo eboniswe kulo mbhalo obhaliweyo yimpazamo esemgangathweni yentsingiselo.
iziphumo
Ukukhupha I-1: I-Naloxone-eyandulelayo okanye eyaneempawu zangasese ezizezomntu onamaxhala azange zibonwe kumagundane anikwe isondlo esipheleleyo esine-fat-fat chow
Idatha yokutya kunye nobunzima bomzimba
Idatha yokufumana ezi zigundileyo ixelwe ngaphambili [36]. Ukushwankathela ngokufutshane ezo zinto zifunyanisiweyo, xa kuthelekiswa namaqela olawulo, iigundane nge-2-h ukufikelela kwansuku zonke kunye nokufikelela kwe-2-h MWF kwindawo yokutya okunesondlo okugqibeleleyo okunamafutha atyhekileyo okugqithisileyo kwixabiso elinokuthengiseka kwi-2 h yokufikelela. Ubunzima bomzimba bezi zilwanyana bonyuswe ngenxa yokutya okukhulu kwaye ke kuncitshisiwe phakathi kokutya okuzinzileyo ngenxa yokuthintela ukuzihluthisa kwemigangatho ye-chow elandelayo xa kulalwa. Nangona kunjalo, ngaphandle kolu tshintsho lobunzima bomzimba iqela linokufikelela kumafutha atyebileyo mihla le lifumana ubunzima obukhulu ngakumbi kuneqela elilawulayo elinomgangatho ofumene ad adum. Ukongeza, xa kuhlalutywa ukuzuza kwesisindo ngexesha lokufunda, bekukho umohluko phakathi kwamaqela (F(3,39) = 7.74, p <0.001), kunye nezo zilwanyana zinokufikelela kwe-2-h yemihla ngemihla kwi-chow enamafutha amnandi ifumana ubunzima obungaphezulu kolawulo oluqhelekileyo lwe-chow (108.6 ± 6.2 g vs. 75.4 ± 3.8 g, ngokulandelelana; p<0.001) kunye nolawulo olunamafutha aswiti-ukutya (88.3 ± 4.9 g; p<0.05). Ukongeza, iigundane ezine-2-h MWF yokufikelela kukutya okunamafutha amnandi zifumene ubunzima ngaphezu kolawulo lwe-chow-fed (95.0 ± 4.6 g vs. 75.4 ± 3.8 g, ngokwahlukeneyo; p<0.05).
Uvavanyo lokurhoxa
Xa unikezwe i-naloxone, kwakungekho mahluko kumanqaku esalathiso sokurhoxiswa kwendlela yokuziphatha ethile ephawulwe phakathi kwamaqela (F(3, 36) = 2.71, p = ns). Ezi ndlela zibandakanya ukungcangcazela kwangaphambi kokugqogqa, ukuwela ikheyi, ukuluma kancinci kunye nokuzikhuselap = ns nganye; yabona Ikhiwane. 1). Ukuqhaqha kwenja emanzi akubonwanga kulo naliphi na iqela.
Amagqabantshintshi ezimpawu ezithile zokurhoxa kulandela ukusweleka kwi-oyile enamafutha amnandi kubonakaliswa Ikhiwane. 2. Akukho nto ibalulekileyo phakathi kwamaqela phakathi kwenqaku elipheleleyo lokurhoxisa amanqaku (F(3, 36) = 2.04, p = ns). Ukuthelekisa-ngobulumko kwe-Pair akuvezi mahluko phakathi kwamaqela e-tremaw, kusolingo okanye ukukhuphela okhuselayo (p = ii-ns zazo zonke). Ukubaluleka kwabonwa phakathi kwamaqela kwiimeko zokuwela i-cage (F(3, 36) = 4.66, p <0.05). Post post Uvavanyo luka-Tukey luveze ukuba i-2-h mihla le ukufikelela kwiigundane kubonakalise iimeko ezimbalwa zokuwela i-cage kunokuba ad adum Iigowuni (p <0.01) okanye ad adum Iirowu ezinamafutha amnandi (p <0.05). Kwakhona, inja emanzi ingcangcazela ayibonwanga kulo naliphi na iqela.
Ukukhupha I-2: I-Naloxone-yangaphambi kwexesha, iimpawu ezizenzekelayo ezizezomntu, okanye iimpawu ezithandekayo zoxinzelelo kwi-maze ephakanyisiweyo azange ziqwalaselwe kwiigundane ezazidliwe ngamafutha amnandi kumgangatho wazo we-chow
Idatha yokutya kunye nobunzima bomzimba
Izilwanyana ezazikwiqela le-12-h i-Sweet-Fat + Chow zasela ukutya okunamafutha amaninzi ngeyure yokuqala yokufikelela kwemihla ngemihla ngokuthelekisa ezo zilwanyana zigcinwe kwi ad adum Ukutya okunamafutha amnandi + kunye neChow (F(2, 21) = 13.16, p <0.001, usuku lwe-28 lokufikelela ekudleni, 5.6 vs. 1.1 g, ngokulandelanayo). Ngomhla wama-28 wokufikelela kokutya, iqela le-12-h Sweet-Fat lisebenzise i-3.5 ± 0.9 g ye-chow, ad adum Iqela leTofi-etyiweyo lithe I0.68 ± 0.7 g ye-op, kunye ad adum Iqela leChow lidle i2.3 ± 1.5 g ye-op kwiyure yokuqala. Ngaphandle kokungafani kokutya kwesiselo esine-fat kunye ne-chow, ngemini ye-28 kwakungekho mahluko ubalulekileyo phakathi kwamaqela kwinani elipheleleyo leekhalori ezisetyenziswe ngexesha le-24-h (F(2, 22) = 0.62; p = ns; I-12-h Imnandi-Amafutha: I-82.8 ± 2.6 Kcal, ad adum Amanqatha amnandi: 77.3 ± 7.8 Kcal, ad adum Chow: 83.2 ± 6.8 Kcal). Ngomhla we-28, ubunzima bomzimba bamagundane babungafani ngokwahlukileyo phakathi kwamaqela (F(2, 23) = 1.87, p = ns). Ngapha koko, uhlalutyo lobunzima obufunyenwe ngexesha lokufunda alwenzi mahluko phakathi kwamaqela (F(2, 21) = 1.31, p = ns).
Uvavanyo lokurhoxa
Kwakungekho mahluko obalulekileyo ngokweenkcukacha-manani zokurhoxiswa kwamanqaku aqatshelwe ngokwamaqela 24 h (F(2, 23) = 0.24, p = ns; Iqela le-12-h le-Fat-Fat iqela = 11.5 ± 2.6, ad adum Iqela leTofi enamafutha = 13.6 ± 2.6; ad adum Iqela leChow = 13.4 ± 1.8) kunye 36 h (F(2, 23) = 0.17, p = ns; Iqela le-12-h le-Fat-Fat iqela = 11.8 ± 2.6, ad adum Iqela leTofi enamafutha = 12.1 ± 1.4; ad adum Iqela leChow = 10.5 ± 2.0) emva kokuba izilwanyana zichithwe kukutya okumnandi. Amanqaku esalathiso abandakanya iindlela zokuzilungisa, ukungcungcuthekiswa yinja emanzi, ukugqobhoza i-cage, ukungcangcazela kwangaphambi kwexesha, ukuluma kancinci kunye nokuzikhusela (kuthelekiso lwesibini ngasinye, p = ns). Akukho zimo zentloko eyayiqwalaselwe kwindawo ye-24 h kunye ne-36 h yamanqaku.
Ngokwe-maze ephakanyisiweyo kunye ne-maze, emva kwe-24 h yokuncitshiswa bekukho umehluko obalulekileyo phakathi kwamaqela ngokwexesha elichithwe engalweni evulekileyo (F(2, 23) = 3.77, p<0.05; 3.1 ± 1.4 s, 20.0 ± 6.0 s kunye no-15.4 ± 4.7 s, ad adum Amanqatha amnandi, i-12-h Imnandi-Amafutha kunye ad adum Chow ngokwahlukeneyo), kunye neempuku ebezigcinwe kuzo ad adum Ukuchitha Amanqatha amnandi ngexesha elincinci kwingalo evulekileyo kune-12-h I-Sweet-Fat group okanye i ad adum Iqela le-Chow (p <0.05). Ku-36 h yokuthotywa, akukho ziphumo zibonwe ngexesha elichithwe kwingalo evulekileyo ye-maze plus (F(2, 23) = 0.22, p= ns; I-26.3 ± 7.6 s, 30.0 ± 10.0 s kunye 23.4 ± 7.2 s, ad adum Amanqatha amnandi, i-12-h Imnandi-Amafutha kunye ad adum Chow ngokwahlukeneyo).
Ukulandela i-naloxone, kwakungekho mahluko mkhulu ngokweenkcukacha-manani zokurhoxiswa kwamanqaku enkcazo yokuziphatha ethile eye yabonwa phakathi kwamaqela (F(2, 23) = 0.64, p = ns). Ukukhutshwa kwezalathiso zesalathiso ezikhutshelweyo yayiyi-8.4 ± 2.5 yeqela le-12-h le-Sweet-Fat group, i-11.5 ± 2.3 ye ad adum Iqela le-Fat-Fat kunye ne-11.4 ± 1.7 ye ad adum Iqela leChow. Amanqaku esalathiso abandakanya indlela yokuziphatha kwamazinyo okuncokola, ukuzilolonga, ukuwela ikheyi, ukungcangcazela kwangaphambili, ukuluma kancinci kunye nokuzikhusela (kuthelekiso lwesibini ngasinye, p = ns). Akukho ziqhushumbo zentloko okanye iinyikima zenja emanzi ziye zaqatshelwa.
Ukukhupha I-3: Iimpawu ze-Naloxone-ezithile ezichongiweyo ezizezomntu okanye iimpawu zoxinzelelo kwi-maze ephakamileyo azibonwanga kwimigundane itya ukutya okunamafutha aphezulu, ukutya okune-sucrose ephezulu
Idatha yokuthatha inxaxheba
Kwiveki yesithathu yokufikelela ekutyeni, bekukho umahluko phakathi kwamaqela ngokwendlela atya ngayo iiyure zokuqala (Iswekile-i-emulsion ye-= = i-32% ye-kcal, uVanilla Qinisekisa = I-27% ye-kcal, kunye ne-10% i-Sucrose = 24% ye-kcal yokutya okwenziwa yonke imihla; F(2, 27) = 39.40, p <0.001). Kwakukho umahluko obalulekileyo ngokweenkcukacha-manani phakathi kwamaqela ngokwemiqathango yokusetyenziswa kwawo kwemihla ngemihla kwirutent chow (F(3, 78) = 22.86, p <0.0001), kunye nezilwanyana ezinokutya okuthandekayo okukhoyo okubonisa ukwehla kokutya okuqhelekileyo kweentonga zomthi ngosuku 28 (23 ± 3 Kcal: Iswekile-ioyile emulsion; 30 ± 4 Kcal: Ukuqinisekisa kweVanilla; 71 ± 2 Kcal: 10% Sucrose ) ngokunxulumene ne ad adum Iqela leChow (101 ± 4 Kcal). Nangona kukho umohluko obonakalayo phakathi kwamaqela ngokwenzeka mihla le kwe-caloric (F(3, 27) = 3.50, p <0.05), ukulandela ukuthelekisa okuninzi kubonise ukuba akukho mahluko ubonisiweyo xa iqela ngalinye lizimele ngokuthelekiswa neqela lolawulo olutya i-chow (101 ± 4 Kcal), p = ns kuzo zonke iimeko (i-118 ± 13 Kcal: I-emulsion ye-iswekile; I-93 ± I-11 Kcal: UVanilla Qinisekisa; i-85 ± I-6 Kcal: i-10% ye-Sucrose). Ngaphaya koko, isixa se-sucrose esinyangiweyo (kwiigramu) sasiguquguquka kuwo onke amaqela iqela ngalinye lisitya i-3-4.5 g yeswekile / yonke imihla, kwanikwa ukutya okwahlukileyo (F(2, 20) = 2.32, p = ns). Ekupheleni kweeveki ze-4, kwakungekho mahluko kwisisindo somzimba phakathi kwamaqela (F(3,31) = 0.25, p = ns). Nangona kunjalo, xa kuhlalutywa ukuzuza kwesisindo ngexesha lokufunda, bekukho umohluko phakathi kwamaqela (F(3,31) = 3.67, p <0.05), kunye nezo zilwanyana zisebenzisa i-emulsion ye-Sugar-oyile ifumana ubunzima obungaphezulu kolawulo lwe-Chow-fed (123 ± 23 g vs. 67 ± 6 g, ngokwahlukeneyo, p <0.05).
Ukurhoxiswa kwedatha
Xa ibekwe kwi-plus-maze ephakanyisiweyo emva kwe-injezone yenalone, izilwanyana ezine-12-h 10% Ufikelelo olufikelelekayo luchithe ixesha elincinci kwingalo evulekileyo ye-plus-maze ngokuthelekiswa nolawulo lweChow-feed (t(9) = 2.58, p <0.05; 52 ± 7 vs. 75 ± 3 s). Akukho mahluko waqatshelwayo phakathi kwamaqela (i-12-h Iqela le-emulsion yeoyile yeqela = 54 ± 11 s kwingalo evulekileyo; I-12-h Vanilla Qinisekisa iqela = 75 ± 3 s kwingalo evulekileyo). Uhlalutyo lwedatha evulekileyo yedatha ye-maze ityhile ukuba i-12-h 10% yeqela le-Sucrose lonyuse umsebenzi we-locomotor (F(3, 29) = 3.65, p <0.05) xa kuthelekiswa ne- ad adum Iqela le-Chow (i-743 ± 70 kunye ne-512 ± I-57 ye-ambulensi yokubala, ngokulandelanayo). Akukho mehluko omnye waphawulwa phakathi kwamaqela kwindawo evulekileyo ye-maze (i-12-h Ishukela-i-emulsion = I-561 ± I-71 ukubalwa kwe-ambulensi; i-12-h Vanilla Qinisekisa iqela = 576 ± 58 ukubalwa kwe-ambulensi).
Ukukhupha I-4: Iimpawu ze-Naloxone-pre-preparised somatic dalili okanye iimpawu zoxinzelelo kwindawo ephakanyisiweyo kunye ne-maze kwimigundane enamafutha amnandi ayizange ibonwe xa kuncitshiswa ubunzima be-85%
Idatha yokutya kunye nobunzima bomzimba
Ukuqala kwiveki yesibini yokufikelela kwamanqatha amnandi, iigundane kwiqela le-2-h lemihla le-Sweet-Fat itya inani eligqithisileyo lweekhalori kwi-2 h yokufikelela kukutya okunamafutha amnandi (i-66.8% yokufumana yonke imihla). nengxelo yethu yangaphambili usebenzisa le modeli [36] kwaye iphakamisa indlela yokuziphatha engafunekiyo yokutya. Iqela le-Acute Sweet-Fat litya i-24.6 ± 12.5 kcal ngomhla we-2 kunye ne-48.1 ± 14.1 kcal ngomhla we-22 okanye i-23 kwi-pellets enamafutha amnandi. Kumanani aqhelekileyo omzimba, amanyathelo aphindaphindiweyo i-ANOVA (ngokulungiswa kweGreenhouse-Geisser) ibonise ukuhlangana kweqela ixesha elininziF(1.63, 27.70) = 21.28, p <0.001). Uvavanyo lwe-post-hoc lubonakalise ubunzima obunzima bomzimba kwiqela le-2-h yemihla ngemihla ye-Sweet-Fat xa kuthelekiswa neqela le-Acute Sweet-fat (usuku lwe-8: t(1, 17) = 2.28, p <0.05, usuku lwe-12: t(1, 17) = 2.63, p <0.05, kunye nomhla we-16: t(1, 17) = 2.94, p <0.01). Ngaphaya koko, xa kwahlolisiswa ubunzima kwiintsuku ezili-16 zokuqala, kwafunyanwa iigundane kwi-2-h yeQela leQatha lamafutha amnandi lifumene ubunzima obukhulu kuneqela le-Acute Sweet-fat group (81.0 ± 4.1 g vs. 45.3 ± 4.5 g, ngokwahlukeneyo; F(1, 18) = 33.83, p <0.001). Xa izilwanyana zancitshiswa kubunzima bomzimba, iisampulu ezibhangqiwe tUvavanyo lubonise ukuba ubunzima bomzimba bawo omabini amaqela ancitshisiwe ngokweenkcukacha-manani (t(9) = 25.50, p <0.001 kunye t(8) = 19.93, p <0.001, 2-h Sweet-Fat Chow kunye ne-Acute Sweet-fat Chow, ngokulandelanayo).
Ukurhoxiswa kwedatha
Kwisisindo esiqhelekileyo, kuphela umahluko okhoyo phakathi kwamaqela uvakalise ukuba i-2-h mihla le iigundane ezinamafutha amnandi ziboniswe kancinci iimeko zokuwela i-cage xa kuthelekiswa namagundane ama-Acute Sweet-fat rats (2.3 ± 0.4 vs. 4.5 ± 0.9, ngokulandelanayo; F(1, 16) = 5.54, p <0.05; Ikhiwane. 3). Nangona kunjalo, akukho mahluko ubonwe kwisalathiso sokurhoxa (i-2-h Imihla ngemihla Amanqatha amnandi: I-9.4 ± 1.2; i-Acute Sweet-fat: 12.5 ± 2.0; F(1, 16) = 2.00, p = ns). Oku kubandakanya amanyathelo okuziphatha okuqhaqha, ukuhlunguzelwa yintloko, ukuzilungisa nokukhulisa (p = ii-ns nganye). Akukho magundane abonakalisiweyo nawaphi na amaxesha okuncokola kwamazinyo.
Kubunzima bomzimba obuncitshisiweyo, kwakungekho mahluko mkhulu ngokwezibalo phakathi kwamaqela kwiimeko ezithile zokuyekiswa, njengoko kubonisiwe kumanqaku esalathiso (F(1, 16) = 0.49, p = ns). Ukukhutshwa kwamanqaku esalathiso yokurhoxa yi-13.0 ± 3.2 kwiqela le-Acute Sweet-fat vs. 10.8 ± 1.2 kwiqela le-2-h lemihla ngemihla yamafutha eSpeed. Inqaku lesalathiso libandakanya indlela yokuziphatha kwamazinyo okuncokola, ukukhulisa, ukuzilolonga, ukuwela ikheyi, ukungcwatywa kwangaphambili, ukuziluma nokuziphatha okuqengqelekayo. Akukho ziimeko zentloko eziye zaqwalaselwa.
Kuvavanyo oluphakanyisiweyo lwe-mer-maze, ixesha elichithwe engalweni evulekileyo lalingafani neqela ngaphambi kokunciphisa umzimba (i-2-h Imihla ngemihla ama-Amanqatha amnandi: I-22.4 ± 7.7 s; I-Acute Sweet-Fat Chow yeqela: I-17.4 ± 11.5 s; F(1, 16) = 0.14, p = ns) okanye emva kokuba unciphise ubunzima (i-2-h Iqela lamafutha atyebileyo emihla ngemihla: I-22.4 s ± 7.0 s; Iqela lamafutha amnandi: I-16.5 ± 7.8 s; F(1, 16) = 0.32, p = ns). Uvavanyo lomsebenzi we-locomotor, kokubini kuqhelekileyo kwaye kuncitshiswe ubunzima bomzimba, kwakungekho mahluko ubalulekileyo phakathi kwe-2-h iigundane zeMihla ngemihla ezinamafutha amnandi kunye namagundane ama-Acute Sweet-Fat ngokwendlela yokusebenza ye-locomotor (Ikhiwane. 4).
Xa kwisisindo somzimba esincitshisiweyo, ngaphandle kweqela, onke amagundane ayesebenza ngakumbi (F(1, 16) = 7.13, p <0.05, Ikhiwane. 4) kwaye uchithe ixesha elingakumbi kwiziko (F(1, 16) = 11.83, p <0.005; I-2-h yemihla ngemihla i-Sweet-Fat: 12.0 ± 1.7 min kubunzima bomzimba obuncitshisiweyo, xa kuthelekiswa ne-9.6 ± 1.6 min kubunzima obuqhelekileyo; Amanqatha amnandi Acute: 12.8 ± 3.2 min kwisisindo esincitshisiweyo xa kuthelekiswa ne-8.8 ± 2.2 min kubunzima bomzimba obuqhelekileyo) kwigumbi lomsebenzi we-locomotor xa kuthelekiswa nokuziphatha kwabo kubunzima bomzimba obuqhelekileyo, kodwa kwakungekho nxibelelene phakathi kobunzima bomzimba neqela.
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Ngokusekwe kwiziphumo zolu vavanyo zine, iigundane ziyayitya into etyiwayo enamafutha kunye noshukela azibonisanga zibonakaliso zibalulekileyo zokurhoxiswa kwe-naloxone okanye ukurhoxa okuzenzekelayo. Kunikwe iziphumo zangaphambili zokuba iigundane ziyayitya iswekile zibonisa iimpawu zokurhoxa kwelexone [9] (eyayiphinda iphindwe apha kwi-Exp. 3), besilindele ukuba iigundane ezine-naloxone zifakwe ngaphandle kokutya okunencasa, etyebileyo ngamafutha ukubonisa iimpawu ezifanayo zokurhoxa. Nangona kunjalo, ukufakwa kwamafutha kukutya kunokuba kuphazamise ukubonakaliswa kweempawu zokurhoxa. Ezi zinto zifunyanisiweyo ziphakamisa ukuba ukurhoxa okufana ne-opiate akujongwa njengokuphendula kukutya okutya okunesondlo, ngakumbi abo batyebileyo ngamafutha, okufana neswekile, eyaziwa ngokuba nefuthe kwiinkqubo zobuchopho. Ke ngoko, ukuvela kwemiqondiso yokurhoxisa efana ne-opiate ebonakalayo ekuphenduleni ekutyeni kakhulu kubonakala kucacisiwe ngqo macronutrient.
Iimpawu zoThintelo lokutya okuphezulu kumanqatha kunye neswekile
Uphengululo lwangaphambili sishwankathele iziphumo zelebhu yethu kwaye abanye bacebisa ukuba ukufikelela iswekile kungakhokelela kwizimo ezininzi zokuziphatha kunye neempawu ze-neurochemical zokulutha kumagundane, kubandakanya ukurhoxa-njengokuthi ukurhoxa kwe-opiate [8, 37]. Kukho izifundo ezisebenzisa imifuziselo yezilwanyana ephakamisa ukuba ukufikelela kwisidlo esityebileyo esinamafutha kungazibethelela ezinye iimpawu zokulutha [16]. Iqela likaCorwin libonisile ukwanda kokuphendula okuqhubekayo kumqolo wokutya amanqatha atya amanqatha, ukucebisa ukuphuculwa okukhuthazayo [38]. U-Bale noogxa bakhe babonisa ukuba iigundane ezigcinwa kukutya okunamafutha amaninzi okanye i-carbohydrate ephezulu kwaye ke kuyaliwe ukufikelela ekutyeni kuya kuhlala kunyanzelekile (ukwehla konyawo) ukuze kufunyanwe ukutya okufunwayo [11]. Ukulandela ukurhoxa okukhulu (ixesha lokuthotywa), iimpuku ezinokufikelela ekutyeni okunamafutha aphezulu zibonisa iimpawu zokuxhalaba kunye nokuchazwa kwento ekhupha i-corticotropin-ukukhulula into kwi-nucleus esembindini ye-amygdala. Nangona kunjalo, uMcGee kunye noogxa bakhe baqaphela ukuba akukho zimpawu zokuxhalaba okanye ukhuthazo oluqhubekekayo usebenzisa ishedyuli yomgaqo oqhubekayo ngokulandela emva kokuthintelwa ekufikeleleni kwimifuno kuncitshiswa imifuno, kufana nokutya ebesikusebenzisa kwiExp. 2 [17]. Ngokudibeneyo, ezi zifundo zicebisa ukuba ezinye iimpawu ezithile zotywala zinokuchaphazeleka xa izilwanyana zinikwa ukutya okunamafutha, kodwa iziphumo zintsokothile kwaye zinokuthi ziphenjelelwe zizinto ezifana nokwenziwa kokutya, ubunzima bomzimba kunye neshedyuli yokufikelela.
Ukucaciswa kweMacronutrient, iFom kunye nokuBakho njengeZinto ekuHambisweni kokuThengiswa kokutya ngokugqibeleleyo
Izifundo ezikhoyo zibandakanya iintlobo ezahlukeneyo zokutya okunamafutha aphezulu, kubandakanya ezinye ezinesondlo esipheleleyo, ezifana "nesidlo." Abanye babezongelwa kukutya okuqhelekileyo okuqhelekileyo, okufana "nokutya okutyayo", okuqhele ukwenziwa ngexesha lokutya kakhulu. [25]. Ukutya nako kwahluka ngokobunjani, ukusuka kukutya okuxheliweyo kwi-Exp. I-1, incindi yokuqina yokutya eyongeziweyo kwi-Exp. I-2 kunye nokutya okulamanzi kwi-Exp. 3. Ukutya okuthe tyibilili kwasetyenziswa ngenxa yobudlelwane obuchongiweyo phakathi konokutya okuthe tyibilili kokutya kunye nokufumana ubunzima kamva31, 32]. Kananjalo, ngenxa yokuba izifundo zethu zangaphambili zibonakalisa ukurhoxiswa okufana nokupheliswa kwempendulo yokufikelela kwi-sucrose isisombululo se-sucrose (siphindaphindwe apha kwi-Exp. 3 apho izilwanyana ezizilambisayo zitya i-sucrose zichitha ixesha elincinci kwingalo evulekileyo ye-maze kwaye zibonise iimpawu zokurhoxa) uxinzelelo lwengqondo Sivavanye i-oyile engamanzi ukubona ukuba ngaba uhlobo lokutya lunokuba nefuthe ekuvakalisweni kokuziphatha okuhambelana nokuyeka. Nangona kunjalo, ukufikelela kulwelo olunamafutha amaninzi akukhange kubonise zimpawu zokurhoxa. Ukusuka kolu hlobo lokutya okutyebileyo kunye nefom, sigqiba kwelokuba ngaphandle kohlobo lokutya okutyebileyo okunamafutha okanye uhlobo olunikiweyo ngalo, uvavanyo lwangoku alukhange lubonakalise iimpawu ezicacileyo zokurhoxa okunjengokuphuma kwezilwanyana kwizilwanyana ezinokutya okungamafutha.
Omnye ubuqhetseba obuthathelwe ingqalelo kolu phononongo yayilixesha lokufikelela. Ezinye iigundwane zazinikwa i-12-h ukufikelela kwemihla ngemihla kwizidlo ezityiwayo, ngelixa ezinye zinikwa ukufikelela kwe-2-h kwishedyuli yemihla ngemihla okanye yexeshana. Zombini ezi ntlobo zokungena kuthintelwe kubonisiwe ukuba zilungiselele indlela yokutya ngokutya okungafunekiyo [8, 39]. Ukusetyenziswa kwe-Binge kubonisiwe ukubangela utshintsho kwiinkqubo zembuyekezo yobuchopho, ngakumbi inkqubo ye-dopamine, ebantwini bobabini [40] nakwimodeli yeereyithi, ezo ziyelelene kwiziphumo ezibonwe ngamachiza athile okuhlukumeza [8]. Nangona ezi shedyuli zokungena zibonisiwe zikhokelela ekutyeni kakhulu, nto leyo yaqinisekiswa kuvavanyo lwangoku, akukho naliphi na ixesha lokufikelela kuvavanyo olukhokelela kwimpawu ezifana nokurhoxa ukuphendula kumanqatha.
Ingcaciso yokuFunyanwa okuKhanyayo kwiiPhononongo zangoku
Ngelixa, idatha ibonakalisa ukuba iimpawu zokurhoxa-njenge-opiate aziveli xa iigundwane zinikezelwa ngokufikelela okunesiseko sokutya okunamafutha, kukho iziphumo ezithile ezilungileyo ezifunyenwe kuseti lwangoku lovavanyo lweengxoxo eziqinisekisiweyo. Kwiphepha I-1, emva kwe-46 h yokuhlutha iswekile enamafutha amnandi, iigundane ezazifumene i-2 h ukufikelela zabonisa iimeko ezimbalwa zokuwela i-cage xa kuthelekiswa ad adum ulawulo olufumileyo (i-rodent chow esemgangathweni okanye amanqatha aphezulu, i-rodent chow). I-Hypoactivity iphawulwe ngexesha lokurhoxiswa kwe-cocaine kwiintonga [41]. Nangona kunjalo, akukho zimpawu zokurhoxiswa okufana ne-opiate ziye zachongwa kwezinye iimvavanyo ezenziwe kweli qela, njengamanyathelo athile okurhoxa.
Kwiphepha I-2, emva kwe-24 h yezilwanyana ezihluthayo ad adum ukufikelela ekutyeni okunamafutha amnandi kuboniswe ukunciphisa ixesha elichithwe kwingalo evulekileyo yomgangatho ophakamileyo wokuphakama. Oku kufumanisa kunomdla, njengoko kubonisa ukuba neqela elinayo ad adum Ukufikelela ekutyeni okuthandekayo kubonise utshintsho kwindlela yokuziphatha ehambelana nokurhoxa. Nangona kunjalo, xa kuvavanywa kwi-36 h, isiphumo besingasabonakali. Oku kungabangelwa kukuba kukho iwindow ethile yexesha apho kuvela khona ngokuzenzekelayo iimpawu zoxinzelelo, kwaye ixesha liphelelwe lixesha lovavanyo olulandelayo. Okanye, inokucebisa ukuba ukusetyenziswa okuphindaphindiweyo kwe-maze yokuphakanyiswa edibeneyo kuguqule intsebenzo kuvavanyo. Ngelixa ezinye izifundo zicebisa ukuba ukuvezwa okuphindaphindiweyo kwi-maze ephakanyisiweyo akuchaphazeli isiphumo sovavanyo [42, 43], abanye banika ingxelo yento yokuhlala [44-47]. Kwiseti yangoku yezifundo, ubukhulu becala akukho mehluko ubonwe phakathi kwamaqela kuxinzelelo, okunokwenzeka kubonise ukuba akukho mahluko ungako ngokuboniswa okuphindiweyo. Nangona kunjalo, i-positive nge ad adum-izilwanyana ezinamayeza kwi-Exp. I-2 kufuneka ithathelwe ingqalelo kwimeko yokusetyenziswa okuphindaphindiweyo koluvavanyo.
Umsebenzi woBunzima bomzimba ekuHlalisweni kweeMpawu zoTywala
Kwisifundo esikhoyo, sivavanye ukuguquguquka kokutya okulunge kakhulu kunye nobunzima bomzimba, zombini kubonisiwe ukuba negalelo kwimibonakaliso efana nokulutha. Amanye amaqela abonise ukuba xa iigundane zinikwa ukufikelela okuthe tye kokutya okumnandi, itshokholethi, ziyotyeba kwaye zibonise indlela yokuziphatha enesifo xa kukhathalelwa ukufikelela kukutya okuthandekayo15]. Izifundo zethu zangaphambili zibonakalisa ukungahambelani okufana nokuziphatha kwizilwanyana ezigcinwe kwi-sucrose yokungena, kwisisindo esiqhelekileyo. Ezinye iziphumo ziye zabonisa ukuba izilwanyana ezityebileyo kunye ad adum okanye ukufikelela okulinganiselweyo kwindlela yokutya yesitayile se-cafeteria bonisa ukusilela kwi-mesolimbic dopamine neurotransmission [18, 48], kodwa izilwanyana ezinokufikelela okungathintelwanga (okt, ukufikelela kokunxunguphala) ezazingacaciswanga njenge-obese azibonisanga dopamine i-2 receptors. Oku kugxininisa umbono wokuba ukutyeba ngokwako kunokubangela utshintsho kwinkqubo yomvuzo wobuchopho [18]. Kwelinye icala, izifundo zabantu abanengxaki yokutya kakhulu zibonisa ukuba ukutya okuzinkcinkca kakhulu, nokuzimela, kukuchaphazela iinkqubo zetheko le-DA [40], ngaloo ndlela kugxininiswa ukubaluleka kokufunda izinto eziguquguqukayo ezithile zokutya kakhulu nokutya kakhulu, kokubini kunye nangokuzimeleyo. Kwiphepha langoku, asikhange sibone iimpawu zokurhoxa okufana ne-opiate kuphuma kwiigundane eziye zanyanzelwa kukutya okutyebileyo ngamanqatha (Exp.1). Kuba izifundo zangaphambili zibonisa ukuba ukutyeba kakhulu kunokubangela utshintsho olufana nolwengqondo, olunokuthi okanye olunokuthi lungabandakanyi zibonakaliso zokurhoxa okunjenge-opiate, kunokwenzeka ukuba sinokuba nakho ukubona okwahlukileyo (okt, okunxulumene ne-opiate) Iimpawu zokurhoxa kwezi zigundane.
Kwiphepha I-4 sivavanye isiphumo sokunciphisa umzimba ngokuvela kweempawu zokurhoxa. Amagundane anembali yokuncitshiswa kokutya ngokukhawuleza afumane ukuzilawula kwe-cocaine xa kuthelekiswa nolawulo [49], kunye nokunciphisa ubunzima kubonisiwe ukuba kuphucula iziphumo zomvuzo weziyobisi [26]. Ukunciphisa iintsimbi zomzimba 'wegundane kukhokelela ekunciphiseni kwamanqanaba e-DA kwi-NAc ukuya kwi-33% yamanqanaba asiseko [50, 51]. Ngaphambili siye safumanisa ukuba xa amanqanaba omzimba egundane enembali yokutya iswekile ancitshiswa abe yi-85%, ukukhutshwa kwe-DA ekuphenduleni iswekile kuyandiswa ngakumbi [27]. Ngezi zizathu, siye saqonda ukuba ukunciphisa amanqanaba omzimba weerats kunokuphucula ukubonakaliswa kokurhoxa. Nangona kunjalo, kwi-Exp. I-4, izibonakaliso ezichaziweyo ze-naloxone zokurhoxisa azizange ziqwalaselwe xa iigundane zincitshisiwe ukuya kwi-85% yobunzima bomzimba oqhelekileyo.
Njengomlinganiselo ongezelelweyo wexhala, sivavanye umsebenzi we-locomotor. Umsebenzi owandisiweyo we-locomotor unxulunyaniswa nokurhoxiswa kweziyobisi [52-54], kwaye yafunyanwa kwi-Exp. I-3 kwiigundane ziyayitya iswekile, kodwa ingekho kumagundane ngokufikelela okunqatha kumanqatha. Ngapha koko, kwi-Exp. I-4, kwakungekho mahluko mkhulu phakathi kwamagundane atya amanqatha kunye nokulawula iigundane ngokwe-locomotion, nokuba kuqhelekileyo okanye kuncitshiswe ubunzima bomzimba.
isiphelo
Amagundane agcinwe kukutya okulunge kakhulu atyebileyo eneswekile kunye namafutha akakhange abonakalise zimpawu zokurhoxa okufana nokuhlutha, ubunzima obuqhelekileyo, okanye ubunzima obuphantsi, kusetyenziswa iindlela eziqinileyo nezilwelo zokutya. Ezi ziphumo zahlukile kwiziphumo zangaphambili ezivela kule labhoratri, kunye nezinye, ezibonisa u-opiate-kurhoxisa-njengokuziphatha kwiigundane ezizingela ukutya iswekile. Iziphumo ezifumanekayo zixhasa umbono wokuba iimpawu zobuthathaka ekuphenduleni ukutya okuninzi kunokutya okunesondlo, ukugxininisa ukubaluleka kokuphanda kwakhona umahluko weziphumo zokutya okunezondlo ezithile kunokuba nakho kwiinkqubo zembuyekezo yobuchopho.
Amagqabantshintshi ophando
- Izifundo zibonisa i-neurochemical kunye neendlela zokuziphatha zeziyobisi xa izilwanyana zitya ukutya okunamafutha kakhulu.
- Ukurhoxa okumiselweyo kweNaloxone akuzange kubonwe kwi-ringe binge kusisitya iintlobo-ezinamafutha aphakamileyo, ukutya okumnandi.
- Ukurhoxa okususwayo ngaphandle kokubonwa akukhange kubonwe kwimigundane yokutya ukutya okunamafutha ahlukeneyo, ukutya okumnandi.
- Ukwehla kobunzima bomzimba, owaziwa ngokuba nefuthe lokunyanzeliswa kwempembelelo yokuxhatshazwa, awuzange uchaphazele neempawu ezikhutshwa yi-naloxone yokurhoxa kwe-opiate-like.
- Iigundane ezizilambatha zitya ukudibanisa amanqatha amnandi azibonisi zimpawu zokurhoxa-okufana nokuyeka phantsi kweemeko ezisetyenzisiweyo.
Imibulelo
Olu phando luxhaswe sisibonelelo se-USPHS i-AA-12882 (BGH) kunye ne-DK-079793 kunye ne-National Eating Disways Foundation (NMA).
Imihlathi
Iphepha elichazayo ukuba awusenanto oyifunayo: Le fayili yeFayile yombhalo wesandla ongabhalwanga owamkelwe ukushicilelwa. Njengenkonzo kumakhasimende ethu sinika le ngcaciso yokuqala kwincwadi yesandla. Umbhalo wesandla uza kufumana ukukopishwa, ukufakela, nokuphonononga ubungqina obunokubakho ngaphambi kokuba kukhutshwe kwifomu yayo yokugqibela. Nceda uqaphele ukuba ngexesha lokuveliswa kweeprogram ezinokuthi zifumaneke ezinokuthi ziphazamise umxholo, kunye nazo zonke izisemthethweni ezichasayo ezisetyenziswa kwiphephancwadi.
Ucaphulo
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